Compositions and Methods for Prognosis and Treatment of Neoplasm

1. A method of assessing the prognosis for a patient who has been diagnosed with, or is suspected to have, a neoplasm, the method comprising: (a) exposing cells derived from a neoplastic tissue sample from the patient to two binding agents under conditions sufficient to allow the binding agents to bind pre-selected markers within the cells, wherein a first binding agent specifically targets mitotic cells and a second agent specifically targets proliferating cells; (b) exposing the cells in step (a) to detection reagents suitable for visualizing and discriminating between proliferating cells that are mitotic and proliferating cells that are non-mitotic; (c) determining the ratio of mitotic cells to proliferating cells (M:P ratio); (d) providing a prognosis based on the M:P ratio and the type of neoplasm, (e) processing a neoplastic tissue sample or cancer cells from the patient in a form suitable for visualization and demarcation of cell nuclei, individually distinguishable centrosomes (iCTRs) and megacentrosomes (mCTRs) in a region of interest (ROI) defined by a plurality of cell nuclei, wherein the neoplastic tissue sample can be the same sample in step (a) or a different sample from the sample in step (a); (f) determining the numbers of iCTRs and mCTRs associated with each cell nucleus in the ROI; (g) determining the volume of each iCTR and mCTR in the ROI; and (h) calculating one or more centrosome amplification scores (CASs) values for the sample based on steps (f) and (g), wherein the neoplasm is Luminal B subtype breast cancer or triple negative breast cancer (TNBC), and wherein an M:P ratio above a predetermined threshold indicates a worse prognosis, and wherein the M:P ratio and the one or more CASs provide a measure of a level of risk and/or a prognosis associated with the cancer and indicate the severity of the cancer, the degree of intratumoral heterogeneity, or both.

2. The method of claim 1 , wherein the method further comprises the step of determining a grade of the cancer, based on stratification provided by the M:P ratio.

3. The method of claim 1 , wherein step (c) comprises flow cytometry to determine the percentages of mitotic cells and proliferating cells.

4. The method of claim 1 , wherein the first binding agent targets a phosphorylated form of histone H3 and wherein the second binding agent targets Ki-67.

5. The method of claim 1 , wherein the patient is treated with at least one antineoplastic agent based on the results from step (d).

6. The method of claim 5 , wherein the at least one antineoplastic agent is selected from the group consisting of anti-mitotic agents, anti-interphase agents, anti-microtubule agents, anthracycline-based agents, and aromatase inhibitor agents.

7. The method of claim 1 , wherein the patient is treated with at least one antineoplastic agent based on the results from steps (d) and (h).

8. The method of claim 1 , wherein the patient is diagnosed with TNBC and wherein the M:P ratio is used to stratify TNBC into high cycling kinetics subclass or low cycling kinetics subclass.

9. The method of claim 1 , further comprising the step of: treating the patient with chemotherapy.

10. The method of claim 1 , further comprising the step of: treating the patient with chemotherapy and at least one additional antineoplastic agent.